Introduction and Objectives OPEP devices can be used to manage a number of different respiratory conditions by providing airway clearance therapy to mobilize and clear excess mucous from the lungs. This assessment investigated the relative importance of a number of different patient relevant features when selecting an OPEP device. Methods The survey was completed, as part of an independent clinical assessment of an OPEP device (Aerobika*, Trudell Medical International), across 23 UK centres by respiratory physiotherapists. They were asked to note, for each patient, the respiratory condition being managed and to select which device features would be important when selecting an OPEP device for that patient. Up to fourteen different features could be selected and these covered topics related to a) ease of use/cleaning, b) clinical adaptability/evidence and c) device robustness/quality. Results Data related to 156 individual patients was collected, covering CF, bronchiectasis and COPD conditions. The most important features noted were generally related to device ease of use and associated attributes. These were highest overall and for each specific respiratory condition. Orientation independence and the ability to easily take apart and clean were identified specifically as high rating factors. When the data was analysed by respiratory condition and the top 5 features compared, there was generally agreement across different conditions, although interestingly the attribute 'clinically proven' was of a greater relative importance when selecting for COPD and bronchiectasis patients than for CF and the ability to use at low expiratory flows was higher rated for COPD than the other two conditions. Conclusions In conclusion, the results reflect the pragmatic and clinically relevant perspective of selecting a device that a patient can easily use and therefore is more likely to use in the real world. Please refer to page A192 for declarations of interest related to this abstract.

RationaleCOPD is a chronic and progressive disease and requires self-administration of inhaled medications. As the disease progresses, reduced respiratory muscle strength may affect patients generating sufficient inspiratory effort to effectively use DPIs.MethodsSymbicort*(100 µg budesonide (BUD)+6 µg formoterol fumarate (FF)) inhaled via either DPI (Turbuhaler,n= 5) or MDI (Vannair,n= 5) with an AeroChamber Plus* Flow Vu* VHC (Trudell) was assessed. 10 males ranging in age from 57–83 inhaled from placebos of their medication. Inhalation profiles were recorded, and later recreated via breathing simulator, coupled to the mouthpiece of the inhaler via an adult oropharynx (OP) model. The simulator was located distal to a collection filter, at the exit of the OP, capturing medication likely to have deposited at the carinal region and potentially available for delivery to the lungs.ResultsThe mass (µg) of FF and BUD recovered from the model OP and filter (CARINA) from each simulation are summarized in table 1. The mass of APIs retrieved from the CARINA for MDI+VHC was greater than the outcomes obtained by simulating the DPI profiles (p ≤ 0.03).ConclusionsThese data indicate the MDI+VHC can deliver more medication than the DPI evaluated to the carinal region. They also demonstrate a need for continued patient inhaler assessment to ensure they can generate the necessary inspiratory effort for sufficient drug delivery

Introduction and objectives Laboratory evaluation of VHC-facemask add-ons is ideally undertaken simulating conditions of use. We report a study in which VHC-facemask add-on devices for infants and small children use were evaluated using anatomical models. Methods 2 VHCs with facemask (n=3 devices/group) were evaluated using anatomical models comprised of airway replicas commensurate with that of a 7 month old infant and 4 year old child. Each VHC was prepared to manufacturer instructions, then evaluated by breathing simulator (ASL5000), mimicking a short coordination delay of 2 s followed by age appropriate tidal breathing. The facemask was attached to ADAM-III infant and child anatomical models. The airways were coupled directly to the breathing simulator via a filter below its exit to capture drug particles that would penetrate as far as the carina in a real patient. 5-actuations of fluticasone propionate (50 µg, FP) were delivered at 30 s intervals. FP recovered from various locations in the aerosol pathway was subsequently assayed by HPLC-UV spectrophotometry. Results The distribution of recovered FP from each type of VHC is summarized in table 1. Conclusions Significantly more FP was delivered to the model ‘carina’ from the AC Plus VHC (p<0.001), the increased mass counterbalanced by decreased retention of medication within the VHC. It is important that clinicians are aware that large differences in delivery efficiency may exist when a facemask is present and some VHCs may fail to deliver any medication in certain cases.Abstract M33 Table 1 FP (mean μg ±SD) recovered from VHCs and Models following tidal breathing Breathing Pattern Child Pattern 155 ml , 25 bpm, 1:2 I:E Infant Pattern 50 ml , 30 BPM, 1:3 I:E Retention Location Free Breathe AeroChamber Plus Flow-Vu Free Breathe AeroChamber Plus Flow-Vu VHC 34.2±2.8 17.5±1.6 40.5±3.7 20.3±1.8 Facemask 1.1±0.6 1.4±0.2 0.0±0.0 1.4±0.2 Airway 0.3±0.2 1.1±0.2 0.0±0.0 0.5±0.1 Filter at ‘Carina’ 5.5± 1.8 10.1± 1.0 0.0±0.0 3.0± 0.9

AimInhaled corticosteroid medication is the gold standard for the treatment of underlying inflammatory disease associated with asthma. Valved holding chambers (VHCs) are often prescribed to optimize fine particle delivery to the lungs whilst minimizing oropharyngeal deposition which is associated with both topical and systemic adverse events. Large volume VHCs have capacities greater than can be emptied in a single breath. This laboratory-based study compared a widely prescribed large and small volume VHCs for the delivery of pMDI-delivered fluticasone propionate (FP).MethodThe large and small volume VHCs (n=3 devices/group) were represented by the 750 mL Volumatic* and 149 ml antistatic AeroChamber Plus* Flow-Vu* VHC. Each VHC was connected to a breathing simulator mimicking a tidally breathing adult (tidal volume=500 mL, rate/min=13; inspiratory: expiratory ratio 1:2). A filter collected the medication delivered at the exit of the chamber. 1-actuation of FP (125 mg/actuation) was delivered to the VHC, and the mass collected on the filter after 1 complete breathing cycle (n=5 replicates) was assayed by HPLC. The procedure was repeated after 2, 3, 5, 8 and 10 breathing cycles.ResultsPerformance measures (mean ±S.D.) are summarized in table 1. Differences in particle transport through the two different sizes of VHC investigated may have been partly responsible for the observed behavior. Another possible explanation for the lower and erratic performance with the Volumatic VHCs relates to the likely presence of electrostatic charges acquired on the internal surface of that VHC through normal handling even though pre-washing was undertaken. Other potential reasons for variability in data may relate to inhalation valve performance.ConclusionsAn effective VHC should be able to deliver sufficient medication in as few inhalations as possible and maintain the availability of medication for inhalation if multiple inhalations (and therefore more time) are required to empty. Using the smaller volume VHC appears to enable a larger and quicker delivery in this study.

Introduction and ObjectivesLaboratory evaluation of VHC-facemask add-ons is ideally undertaken simulating conditions of use. We report a study in which such devices for small child use were evaluated using an anatomical face-model and upper airway commensurate with that of a 4 year old child.MethodsA number of VHCs with facemask (n=3 devices/group) were evaluated using an anatomical face-model and upper airway commensurate with that of a 4 year old child. Each VHC was prepared to manufacturer instructions, then evaluated by breathing simulator (ASL5000), mimicking a short coordination delay of 2 s followed by tidal breathing (tidal volume (Vt)=155 mL, I:E ratio=1:2, rate=25 cycles). The facemask was attached to ADAM-III small child model. The airway was coupled directly to the breathing simulator via a filter below its exit to capture drug particles that would penetrate as far as the carina in a real patient. 5-actuations of fluticasone propionate (50 µg, FP) were delivered at 30 s intervals. FP recovered from various locations in the aerosol pathway was subsequently assayed by HPLC-UV spectrophotometry.ResultsDistribution of recovered FP from each type of VHC is summarised in Table 1.ConclusionsSignificantly more FP was delivered to the model ‘carina’ from the AC Plus VHC with child mask (p<0.001), the increased mass counterbalanced by decreased retention of medication within the VHC. It is important that clinicians are aware that large differences in delivery efficiency may exist when a facemask is present.

Introduction and ObjectivesPriming VHCs with several actuations of medication before use may be an established practice to prepare the spacer before use. However this practice can have a significant influence on subsequent medication delivery. The present study set out to test the hypothesis that priming is not effective, or better than the use of anti-static materials.MethodsThe following VHCs, each with mouthpiece as patient interface (n=5 devices/group) were evaluated: AeroChamber Plus Flow-Vu Antistatic VHC (AC +FV AVHC); AeroChamber Plus; Volumatic…; Able Spacer 2…; Anti-Static Compact Space Chamber plus…. Each VHC was connected via a filter holder to a vacuum source operated at 28.3 L/min, evaluated with a pMDI (Flovent 125 µg, FP) and the Emitted Mass of FP (EMFP) determined by HPLC-UV assay. The following sequence of testing was conducted: 1) Test VHC immediately after removal from packaging (no pre-treatment) and evaluate EMFP following one actuation. 2) Supply two more actuations into the same VHC and evaluate EMFP (representing 3 actuations of priming).3) Deliver 17 more actuations into the same VHC and evaluate EMFP (representing priming of 20 actuations). 4) Clean VHC, then repeat part (1) (representing pre-conditioning by washing as an alternative to priming).ResultsThe behaviour of EMFP (mean ±SD) with VHC type is summarised in figure 1.ConclusionsClinicians should be aware that priming of VHCs Results in inconsistent medication delivery, and is wasteful of medication.

The National Marrow Donor Program (NMDP) projects the need for allogeneic unrelated blood and marrow transplants (BMT) in the United States is 10,000 per year. While the NMDP is preparing to facilitate that number by 2015, there are a number of barriers to meeting this need including recruiting additional health care personnel including BMT providers. To learn how best to recruit BMT physicians, we sought to understand why practicing BMT physicians chose to enter BMT, and why others did not. We conducted a web-based survey amongst Pediatric Hematology/Oncology (PHO) and BMT physician providers and trainees to determine the factors influencing their decision to choose or not choose a career in BMT. There were 259 respondents (48% male, 74% of Caucasian origin); 94 identified as BMT physicians, 112 as PHO physicians and 53 as PHO trainees. PHO and BMT providers spent an average of 53% in clinical activities. More than 2/3 of PHO providers stated that they provide BMT services at their institutions, most commonly inpatient coverage (73%). The proportion of providers exposed to BMT early in their training was significantly higher amongst BMT providers than PHO providers (51% vs. 18% during medical school [p<0.0001] and 70% vs. 50% during residency [p < 0.005]). Exposure during fellowship (94%) did not differ amongst groups. The decision to pursue a career in BMT was made before fellowship (medical school or residency) in 50% of the respondents. A lower proportion of BMT providers reported currently being involved in education of medical students and residents compared to PHO providers (98% vs. 76%, p<0.0001). Of 53 trainees, 64% reported that they were not contemplating a career in BMT. Of these, 68% stated that inadequate exposure to BMT prior to PHO fellowship was the reason. Only 26% reported BMT exposure in medical school and 43% during residency. The two most common reasons for the choice of a BMT career were the degree of intellectual and scientific challenge (89%) and role models/mentors in the field (67%). This survey suggests that early exposure to BMT during medical school and residency results in increased interest in pursuing a career in BMT. BMT physicians and training program directors can foster interest in the BMT field by promoting BMT focused education and clinical inpatient and outpatient rotations during medical school and residency. This early exposure to BMT may aid in a higher recruitment of future transplant providers.

The objective of this study was to examine the pharmacokinetics of intravenous dalteparin (Fragmin, Pharmacia-Upjohn, Peapack, NJ) and to assess the accuracy of standard coagulation-based monitoring techniques as an estimate of drug concentration with which to guide dosing. Knowledge of the kinetic behavior of low-molecular-weight heparins (LMWHs) and the possible utility of coagulation times for monitoring may aid in the development of safe and effective dosing algorithms for percutaneous coronary interventions. Twenty normal volunteers were treated at 2-week intervals with each of three intravenous dalteparin doses. Measurement of anti-IIa, anti-Xa, activated partial thromboplastin time (aPTT), activated clotting time (ACT), and low-range ACT was performed at baseline and at seven additional time points over 8 hours. The half-life of intravenous dalteparin is 77 minutes with slight dose-related variation. The aPTT, LR-ACT, and standard ACT are prolonged after dalteparin administration with the increase closely correlated to anti-Xa activity (aPTT, r = 0.85; LR-ACT, r = 0.79). Classification of anticoagulation intensity range using aPTT or LR-ACT in comparison to anti-Xa activity (0.5-0.99, 1.0-1.49, 1.5-2, >2) displays a level of agreement (kappa: aPTT = 0.69, LR-ACT = 0.59) that is comparable to values reported for coagulation time guidance of unfractionated heparin administration. Standard coagulation times are sensitive to the anticoagulant effect of dalteparin with a degree of correlation that suggests their utility for estimating drug concentration during high dose therapy. Trials establishing a relationship between monitoring and clinical efficacy, and the risk/reward of different treatment ranges alone or in combination with GPIIb/IIIa inhibitors and clopidogrel, are necessary.